• Toxicological Research
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• 제14권3호
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• pp.365-370
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• 1998

To evaluate the renal toxicity of the antitumor agent, p-{N,N,-Bis(2-chloroethyl)amino}-4-phenyl acetyl-amino-2,6-piperidinedione(CK-15), rats were treated with CK-15 (acute: 50mg/kg. i.p., single and subacute: 5mg/kg, i.p., daily for 7 days). The changes in the body weight, water consumption, kidney weights and urine volume after and during the treatment were observed. The concentrations of urinary creatinine and portein, the activities of N-acetyl-${\beta}$-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), ${\gamma}$-glutamyl transpeptidase (${\gamma}$-GT) and lactate dehydrogenase (LDH) in 24hr urine were also determined. The body weight, water consumption, and urine volume were decreased after the acute and subacute administration. However the weights of kidney were not changed after the treatments. The excretion of creatinine was significantly decreased 1 day after acute administration but, returned to the control value. In subactute administration, the excretion of creatinine was gradually decreased. However, the protein excretion did not changed in both treatment. Those indicate that CK-15 might decrease the metabolic rate of muscle. THe urinary activities of NAG, AAP, ${\gamma}$-GT, and LDH were significantly affected bythe drug treatment. The urinary activities of NAG, AAP and ${\gamma}$-GT were significantly increased 1 day after the acute administration and then returned to the control value. However, the urinary activities of LDH were not changed in acute treatment. In subacute treatment, although the urinary activities of NAG were not changed, those of AAP and ${\gamma}$-GT were significantly increased 2.3 times at 3 days during the subacute administration. Also the urinary activities of LDH were significantly increased at 7 day after the administration. These results indicate that the high and subacute administration might induce a damage in the kidney cells. Furthermore the present results suggest that the toxic effects of CK-15 might be due to the accumulation of the metabolites.

• 약학회지
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• 제41권3호
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• pp.283-293
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• 1997

Some analogs and their Mannich bases of Antineoplaston A10 (A10) were synthesized. Chemical yield for the 2-(or 3-)thienyl, benzol, and phenylpropionyl analogs were high but 1-naphthyl analog was synthesized in low yield. The Mannich bases formation of these analogs with morpholine went verywell compared to other bases. 1-Naphthyl, 4-nitrobenzoyl, and phenylpropionyl analogs of A10 showed weak in vitro activity but the other A10 analogs showed weaker or no activity at 10-1000mcg/ml. But their Mannich bases containing A10analogs showed good in vitro activity compared to simple A10 analogs.